Publication details

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Authors	KUDO M. GALLE P. R. LLOVET J. M. FINN R. S. VOGEL A. MOTOMURA K. ASSENAT E. MERLE P. BRANDI G. DANIELE B. OKUSAKA T. TOMÁŠEK Jiří BORG C. DADDUZIO V. MORIMOTO M. PRACHT M. JEN M. H. UBREVA N. D. WIDAU R. C. SHINOZAKI K. YOSHIKAWA R. ZHU A. X.
Year of publication	2020
Type	Article in Periodical
Magazine / Source	Liver International
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/liv.14462
Doi	http://dx.doi.org/10.1111/liv.14462
Keywords	alpha-fetoprotein (AFP); elderly; hepatocellular carcinoma; ramucirumab; sorafenib intolerance; VEGFR2
Description	Background & Aims Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) >= 400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP >= 400 ng/mL by three prespecified age subgroups (<65, >= 65 to <75 and >= 75 years). Methods Individual patient data were pooled from REACH (baseline AFP >= 400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). Results A total of 542 patients (<65 years: n = 302; >= 65 to <75 years: n = 160; >= 75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), >= 65 to <75 years (0.602; 0.419-0.866) and >= 75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity >= 97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. Conclusions In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including >= 75 years.